ArticleAmerican journal of respiratory and critical care medicine2017
Smoking-Dependent Distal-to-Proximal Repatterning of the Adult Human Small Airway Epithelium.
Article in American journal of respiratory and critical care medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
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- FGFR signaling establishes spatial gradients of secretory cell identities along the airway proximal-distal axis.Nature communications · 2026Article
- Airway epithelial heterogeneity and mucus plugging in asthmatic bronchioles.American journal of respiratory and critical care medicine · 2026Article
- When asthmatic distal airways lose their identity: a new mechanism of mucus plugs pathogenesis.American journal of respiratory and critical care medicine · 2026Article
- Spatial single-cell atlas reveals regional variations in healthy and diseased human lung.Nature communications · 2025Article
- Upper and Lower Respiratory Tract Compartmentalization in Pediatric Stem Cell Transplantation.medRxiv : the preprint server for health sciences · 2025Article
- Toward precision medicine in COPD: phenotypes, endotypes, biomarkers, and treatable traits.Respiratory research · 2025Review
- Structure and function relationships of mucociliary clearance in human and rat airways.Nature communications · 2025Article
- NF-κB-mediated EAAT3 upregulation in antioxidant defense and ferroptosis sensitivity in lung cancer.Cell death & disease · 2025Article
- Structure and Function Relationships of Mucociliary Clearance in Human and Rat Airways.bioRxiv : the preprint server for biology · 2025Article
- Airway basal stem cell therapy for lung diseases: an emerging regenerative medicine strategy.Stem cell research & therapy · 2025Review
- Lung Immune Cell Niches and the Discovery of New Cell Subtypes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- A novelThe European respiratory journal · 2024Article
- Unveiling mechanisms of lung aging in COPD: A promising target for therapeutics development.Chinese medical journal pulmonary and critical care medicine · 2024Review
- Genetics and Genomics of Pulmonary Fibrosis: Charting the Molecular Landscape and Shaping Precision Medicine.American journal of respiratory and critical care medicine · 2024Review
- The multiple facets of the club cell in the pulmonary epithelium.Histology and histopathology · 2024Review
- STRUCTURE-FUNCTION RELATIONSHIPS OF MUCOCILIARY CLEARANCE IN HUMAN AIRWAYS.Research square · 2024Article
- Human iPSC-Based Model of COPD to Investigate Disease Mechanisms, Predict SARS-COV-2 Outcome, and Test Preventive Immunotherapy.Stem cells (Dayton, Ohio) · 2024Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
rationaleSmall airways are the primary site of pathologic changes in chronic obstructive pulmonary disease (COPD), the major smoking-induced lung disorder.
objectivesOn the basis of the concept of proximal-distal patterning that determines regional specialization of the airway epithelium during lung development, we hypothesized that a similar program operates in the adult human lung being altered by smoking, leading to decreased regional identity of the small airway epithelium (SAE).
methodsThe proximal and distal airway signatures were identified by comparing the transcriptomes of large and small airway epithelium samples obtained by bronchoscopy from healthy nonsmokers. The expression of these signatures was evaluated in the SAE of healthy smokers and smokers with COPD compared with that of healthy nonsmokers. The capacity of airway basal stem cells (BCs) to maintain region-associated phenotypes was evaluated using the air-liquid interface model. MEASUREMENTS AND MAIN
resultsThe distal and proximal airway signatures, containing 134 and 233 genes, respectively, were identified. These signatures included known developmental regulators of airway patterning, as well as novel regulators such as epidermal growth factor receptor, which was associated with the proximal airway phenotype. In the SAE of smokers with COPD, there was a dramatic smoking-dependent loss of the regional transcriptome identity with concomitant proximalization. This repatterning phenotype was reproduced by stimulating SAE BCs with epidermal growth factor, which was up-regulated in the SAE of smokers, during differentiation of SAE BCs in vitro.
conclusionsSmoking-induced global distal-to-proximal reprogramming of the SAE represents a novel pathologic feature of COPD and is mediated by exaggerated epidermal growth factor/epidermal growth factor receptor signaling in SAE BCs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.